Indirubin, a component of Ban-Lan-Gen, activates CYP3A4 gene transcription through the human pregnane X receptor

Ban-Lan-Gen is the common name for the dried roots of indigo plants, including Polygonum tinctorium, Isatis indigotica, Isatis tinctoria, and Strobilanthes cusia. Ban-Lan-Gen is frequently used as an anti-inflammatory and an anti-viral for the treatment of hepatitis, influenza, and various types of...

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Published in:Drug metabolism and pharmacokinetics 2016-04, Vol.31 (2), p.139-145
Main Authors: Kumagai, Takeshi, Aratsu, Yusuke, Sugawara, Ryosuke, Sasaki, Takamitsu, Miyairi, Shinichi, Nagata, Kiyoshi
Format: Article
Language:English
Subjects:
AhR activator
CYP3A4 induction
Cytochrome P-450 CYP3A - genetics
Cytochrome P-450 CYP3A - metabolism
Dose-Response Relationship, Drug
Hep G2 Cells
Herb–drug interactions
Humans
Indirubin
Indoles - pharmacology
Pregnane X Receptor
PXR
Receptors, Steroid - metabolism
RNA, Messenger - drug effects
RNA, Messenger - genetics
RNA, Messenger - metabolism
Structure-Activity Relationship
Transcriptional Activation - drug effects
Transcriptional Activation - genetics
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Summary:Ban-Lan-Gen is the common name for the dried roots of indigo plants, including Polygonum tinctorium, Isatis indigotica, Isatis tinctoria, and Strobilanthes cusia. Ban-Lan-Gen is frequently used as an anti-inflammatory and an anti-viral for the treatment of hepatitis, influenza, and various types of inflammation. One of the cytochrome P450 (CYP) enzymes, CYP3A4, is responsible for the metabolism of a wide variety of xenobiotics, including an estimated 60% of all clinically used drugs. In this study, we investigated the effect of Ban-Lan-Gen on the transcriptional activation of the CYP3A4 gene. Ban-Lan-Gen extract increased CYP3A4 gene reporter activity in a dose-dependent manner. Indirubin, one of the biologically active ingredients in the Ban-Lan-Gen, also dose-dependently increased CYP3A4 gene reporter activity. Expression of short hairpin RNA for the human pregnane X receptor (hPXR-shRNA) inhibited CYP3A4 gene reporter activity, and overexpression of human PXR increased indirubin- and rifampicin-induced CYP3A4 gene reporter activity. Furthermore, indirubin induced CYP3A4 mRNA expression in HepG2 cells. Taken together, these results indicate that indirubin, a component of Ban-Lan-Gen, activated CYP3A4 gene transcription through the activation of the human PXR.
ISSN:1347-4367
1880-0920
DOI:10.1016/j.dmpk.2016.01.002